The present invention relates in general to the field of ischemic brain injury; and more particularly, to neuroprotective method and composition adapted for the treatment of cerebral ischemia.
Without limiting the scope of the invention, its background is described in connection with the treatment of Ischemic brain injury such as a stroke or a secondary ischemic injury after a brain trauma, with stroke as an example.
Stroke is a severe, often-catastrophic disease affecting approximately 500,000 people per year in the U.S. Present methods of treatment except thrombolysis rely on supportive measures and non-specific agents. Twenty-five to sixty percent of stroke victims experience mild to severe disability, greatly increasing the long-term health related costs with aiding these patients. Therefore, there exists a need for improved methods of treating the morbidity experienced by these patients.
While intravenous thrombolytic treatments have shown promise, they generally require intervention within three hours of a stroke. Other unproven oral drug treatments may be initiated within a 24-hour post-stroke window and may positively affect neurological outcome with continued dosage for three months after a stroke.
One such method of protecting brain tissue from cerebral infarction subsequent to ischemia is disclosed in U.S. Pat. No. 5,827,832, issued to Sandage, Jr., et al. Sandage discloses an invention directed to a method of reducing the extent of infarction, and in particular, cerebral infarction subsequent to cerebral ischemia. Citicoline is administered shortly after an ischemic episode and continuing daily treatment for up to about 30 days, and in one preferred embodiment for at least about 6 weeks. The method taught is used for the treatment of stroke and severe head trauma patients and maximizes the chances for a full or substantially full recovery of the patient. The treatment regimen disclosed, however, uses citicoline, which is an exogenous form of cytidine-5xe2x80x2-diphosphocholine a key intermediate in the biosynthesis of membrane phosphatidyl choline, which is of primary importance for the dynamic regulation of cellular integrity. Furthermore the treatment protocol requires continued treatment for several weeks, with increased cost and likelihood of missing important doses.
Another method for treating central nervous system ischemia is disclosed in U.S. Pat. No. No. 5,571,840, issued to Mayor, et al., in which a patient who has suffered an acute insult is treated by administering an effective amount of a thyroid hormone. The thyroid hormones for use with the invention, as disclosed, include levothyroxine, liothyronine, L-3,3xe2x80x2,5xe2x80x2-triiodothyronine or L-3,5-diiodothyronine, or their sodium salts. The treatment as taught is applicable to the treatment of cerebral ischemia following cardiac arrest. The thyroid hormones, however, have known short and long-term side effects and must be used with great care under a physicians close supervision.
The present invention improves upon this composition to better treat persons with ischemic brain injury as characterized by cerebral ischemia or ischemia associated with, and secondary to, brain injury.
In order to better treat persons with stroke and reduce the associated long-term and high cost of care, there is a need for improved treatment that may be both neuroprotive and able to reduce secondary brain injury associated with stroke. The present invention includes a method and composition adapted for the treatment of stroke. Applications in humans that may benefit from the use of the present invention include post-trauma surgery and other cardiac surgery (e.g., CABG, cardiopulmonary bypass), and persons with spinal cord injury, cerebral or cardiac emboli, cardiac arrest, stroke, subarachnoid hemorrhage, neurodegenerative diseases and combinations, thereof.
Generally, the present invention is a method adapted for the treatment of ischemic brain injury that includes applying hypothermic conditions to a subject after onset of brain injury and administering to the subject in need thereof a dose of a pharmaceutically effective amount of caffeine and a dose of a pharmaceutically effective amount of an alcohol (i.e. an alkanol) or mixtures thereof.
In another form, the present invention is a method adapted for the treatment of ischemic brain injury including the steps of applying hypothermic conditions to a subject within 5 hours after onset of brain injury, wherein said hypothermic condition includes reducing the body core temperature to at about 33-35 degrees Centigrade, and co-administering to the subject in nee d thereof a dose of a pharmaceutically effective amount of caffeine and a dose of a pharmaceutically effective amount of ethanol adapted for the treatment of cerebral ischemia under hypothermic conditions.